Pain
Conditions
Keywords
Pain, Hydromorphone, Acute, Emergency Department
Brief summary
The hydromorphone protocol is more effective than usual care in Emergency Department (ED) patients age 65 years and older in terms of proportion who choose to forgo additional pain medication within 60 minutes post-baseline in the two groups.
Interventions
DRUGHydromorphone
0.5 mg IV hydromorphone followed by an optional 0.5 mg IV dose
DRUGUsual care
Attending administers any IV opioid in any dose he chooses
Sponsors
Montefiore Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
65 Years to 120 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age greater than or equal to 65 years: This is a study of elderly patients. 2. Pain with onset within 7 days: Pain within seven days is the definition of acute pain that has been used in Emergency Department (ED) literature. 3. ED attending physician's judgment that patient's pain may warrant intravenous (IV) opioids: The factors that influence the decision to use parenteral opioids are complex and extensive. An approach that is commonly taken to address the issue of patient selection in drug trials is to use a specific condition (e.g., renal colic) or treatment (e.g., post-hysterectomy) that would generally be thought to be appropriately treated with an opioid analgesic, thereby eliminating individual judgment about eligibility for the study. However in order to assess the role of opioids with the widest generalizability in the ED setting, the investigators decided to enroll patients with a variety of diagnoses, all with a complaint of acute pain. Opioids are not an appropriate treatment for all patients who present with a complaint of pain (e.g., gastroenteritis, migraine). Therefore, unless there is a restriction to patients with a specific diagnosis, either a comprehensive list of diagnoses and situations in which opioids are indicated must be specified, or clinical judgment needs to be used. The investigators have opted for the latter alternative. 4. Normal mental status: In order to provide measures of pain experienced the patient needs to have a normal mental status. The investigators will use a 6-item screener (Wilber 2008) as an indicator of sufficiently normal mental status to participate in the study.
Exclusion criteria
1. Prior use of methadone: the effect of methadone use on the perception of acute pain is unknown and suspected to be altered. The investigators feel that the needs of patients on methadone may exceed the dosage ceiling of 1 mg that will be used for this study. Similar to sickle cell patients and chronic cancer patients, patients on methadone usually require significantly higher doses of opioids to control their pain. Thus, the investigators feel that it would be unethical to restrict the dose that this subset of patients can receive. 2. Use of other opioids or tramadol within past seven days: to avoid introducing bias related to opioid tolerance that may alter the response to the study medication thereby masking the medication's effect. 3. Prior adverse reaction to opioids. 4. Chronic pain syndrome: frequently recurrent or daily pain for at least 3 months results in alteration in pain perception which is thought to be due to down-regulation of pain receptors. Examples of chronic pain syndromes include sickle cell anemia, osteoarthritis, fibromyalgia, migraine, and peripheral neuropathies. 5. Alcohol intoxication: the presence of alcohol intoxication as judged by the treating physician may alter perception, report, and treatment of pain. 6. Systolic blood pressure \<90 mm Hg: Opioids can produce peripheral vasodilation that may result in orthostatic hypotension. 7. Oxygen saturation \<95% on room air: For this study, oxygen saturation must be 95% or above on room air in order to be enrolled. 8. Use of monoamine oxidase (MAO) inhibitors in past 30 days: MAO inhibitors have been reported to intensify the effects of at least one opioid drug causing anxiety, confusion and significant respiratory depression or coma. 9. C02 measurement greater than 46: In accordance with a similar study (04-12-360), three subsets of patients will have their CO2 measured using a handheld capnometer prior to enrollment in the study. If the CO2 measurement is greater than 46, then the patient will be excluded from the study. The 3 subsets are as follows: * All patients who have a history of chronic obstructive pulmonary disease (COPD) * All patients who report a history of asthma together with greater than a 20 pack-year smoking history * All patients reporting less than a 20 pack-year smoking history who are having an asthma exacerbation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Successful Treatment | 1 hour | Number of patients with successful treatment is defined as the number of patients who declined additional pain medication within 1 hour of study entry when asked the question, Do you want more pain medication?. This measure looks at declining pain medication at either 15 minutes or 60 minutes, whereas 4. Post-Hoc refers only to the answer to the question at the 60 minute mark post-baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Pain Intensity From Baseline to 60 Minutes | 60 minutes | Pain intensity is measured on the numerical rating scale (NRS) with scores ranging from 0 (no pain) to 10 (worst pain imaginable). The change in scores over time is calculated by subtracting the score at 60 minutes from the score at baseline (before treatment). These change values were then averaged. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hydromorphone Hydromorphone protocol
Hydromorphone: 0.5 mg IV hydromorphone followed by an optional 0.5 mg IV dose | 153 |
| Usual Care Usual care
Usual care: Attending administers any IV opioid in any dose he chooses | 166 |
| Total | 319 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Erroneously Enrolled Twice | 8 | 2 |
| Overall Study | Missing Data | 5 | 3 |
| Overall Study | Protocol Violation | 9 | 4 |
Baseline characteristics
| Characteristic | Hydromorphone | Usual Care | Total |
|---|---|---|---|
| Age, Continuous | 75 years STANDARD_DEVIATION 7 | 74 years STANDARD_DEVIATION 6 | 74 years STANDARD_DEVIATION 6 |
| Diagnosis Appendicitis | 0 Participants | 6 Participants | 6 Participants |
| Diagnosis Back pain | 14 Participants | 13 Participants | 27 Participants |
| Diagnosis biliary colic/cholecystitis | 6 Participants | 11 Participants | 17 Participants |
| Diagnosis Colitis/diverticulitis | 14 Participants | 10 Participants | 24 Participants |
| Diagnosis Extremity fracture | 11 Participants | 7 Participants | 18 Participants |
| Diagnosis Kidney stone/pyelonephritis | 7 Participants | 11 Participants | 18 Participants |
| Diagnosis Musculoskeletal pain | 24 Participants | 24 Participants | 48 Participants |
| Diagnosis Non-specific abdominal pain | 50 Participants | 57 Participants | 107 Participants |
| Diagnosis Other (pancreatitis, perforated viscus, etc) | 15 Participants | 14 Participants | 29 Participants |
| Diagnosis Small Bowel Obstruction | 12 Participants | 13 Participants | 25 Participants |
| Nauseated or vomited before receiving opioids in the ED No | 87 Participants | 89 Participants | 176 Participants |
| Nauseated or vomited before receiving opioids in the ED Unknown | 1 Participants | 0 Participants | 1 Participants |
| Nauseated or vomited before receiving opioids in the ED Yes | 65 Participants | 77 Participants | 142 Participants |
| Pain Intensity NRS = 10 | 76 Participants | 81 Participants | 157 Participants |
| Pain Intensity NRS = 3-6 | 12 Participants | 13 Participants | 25 Participants |
| Pain Intensity NRS = 7 | 14 Participants | 20 Participants | 34 Participants |
| Pain Intensity NRS = 8 | 31 Participants | 28 Participants | 59 Participants |
| Pain Intensity NRS = 9 | 20 Participants | 24 Participants | 44 Participants |
| Race/Ethnicity, Customized African American | 35 Participants | 44 Participants | 79 Participants |
| Race/Ethnicity, Customized Hispanic | 97 Participants | 103 Participants | 200 Participants |
| Race/Ethnicity, Customized Other | 6 Participants | 3 Participants | 9 Participants |
| Race/Ethnicity, Customized White | 15 Participants | 16 Participants | 31 Participants |
| Region of Enrollment United States | 153 Participants | 166 Participants | 319 Participants |
| Sex: Female, Male Female | 105 Participants | 108 Participants | 213 Participants |
| Sex: Female, Male Male | 48 Participants | 58 Participants | 106 Participants |
| Weight | 162 lbs STANDARD_DEVIATION 33 | 165 lbs STANDARD_DEVIATION 38 | 164 lbs STANDARD_DEVIATION 36 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 153 | 0 / 166 |
| other Total, other adverse events | 27 / 153 | 32 / 166 |
| serious Total, serious adverse events | 0 / 153 | 0 / 166 |
Outcome results
Primary
Number of Patients With Successful Treatment
Number of patients with successful treatment is defined as the number of patients who declined additional pain medication within 1 hour of study entry when asked the question, Do you want more pain medication?. This measure looks at declining pain medication at either 15 minutes or 60 minutes, whereas 4. Post-Hoc refers only to the answer to the question at the 60 minute mark post-baseline.
Time frame: 1 hour
Population: The discrepancy between the number of patients enrolled and randomized and the number analyzed is due to patient never being given IV opioids (13), enrolled twice (10), and missing primary outcome data (8)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hydromorphone | Number of Patients With Successful Treatment | Achieved satisfactory analgesia within 60 min | 127 Participants |
| Hydromorphone | Number of Patients With Successful Treatment | No satisfactory analgesia within 60 min | 26 Participants |
| Usual Care | Number of Patients With Successful Treatment | Achieved satisfactory analgesia within 60 min | 137 Participants |
| Usual Care | Number of Patients With Successful Treatment | No satisfactory analgesia within 60 min | 29 Participants |
Secondary
Mean Change in Pain Intensity From Baseline to 60 Minutes
Pain intensity is measured on the numerical rating scale (NRS) with scores ranging from 0 (no pain) to 10 (worst pain imaginable). The change in scores over time is calculated by subtracting the score at 60 minutes from the score at baseline (before treatment). These change values were then averaged.
Time frame: 60 minutes
Population: The discrepancy between the number of patients enrolled and randomized and the number analyzed is due to patient never being given IV opioids (13), enrolled twice (10), and missing primary outcome data (8)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydromorphone | Mean Change in Pain Intensity From Baseline to 60 Minutes | 5.4 units on a scale | Standard Deviation 2.9 |
| Usual Care | Mean Change in Pain Intensity From Baseline to 60 Minutes | 5.2 units on a scale | Standard Deviation 3.1 |
Post Hoc
Number of Patients Who Achieved Satisfactory Analgesia at 15 Minutes Post-baseline
Satisfactory Analgesia is defined as declining additional pain medication when asked the question, Do you want more pain medication?
Time frame: 15 minutes
Population: The discrepancy between the number of patients enrolled and randomized and the number analyzed is due to patient never being given IV opioids (13), enrolled twice (10), and missing primary outcome data (8)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hydromorphone | Number of Patients Who Achieved Satisfactory Analgesia at 15 Minutes Post-baseline | 89 Participants |
| Usual Care | Number of Patients Who Achieved Satisfactory Analgesia at 15 Minutes Post-baseline | 111 Participants |
Post Hoc
Number of Patients Who Achieved Satisfactory Analgesia at 60 Minutes Post-baseline
Satisfactory analgesia is defined as the patient declining additional pain medication when asked the question, Do you want more pain medication?. This measure refers only to the answer to this question asked at the 60 minute mark. The Primary Outcome (1. Primary Outcome - Number of Patients with successful treatment) refers to the answering no to this question at 15 minutes or 60 minutes post-baseline.
Time frame: 60 minutes
Population: The discrepancy between the number of patients enrolled and randomized and the number analyzed is due to patient never being given IV opioids (13), enrolled twice (10), and missing primary outcome data (8)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hydromorphone | Number of Patients Who Achieved Satisfactory Analgesia at 60 Minutes Post-baseline | 111 Participants |
| Usual Care | Number of Patients Who Achieved Satisfactory Analgesia at 60 Minutes Post-baseline | 119 Participants |
Post Hoc
Number of Patients With 50% or Greater Decline in Pain Intensity Score From Baseline to 60 Minutes
Pain intensity is measured on the numerical rating scale (NRS) with scores ranging from 0 (no pain) to 10 (worst pain imaginable). The 50% or greater change in pain score is measured by subtracting the pain score at 60 minutes from the pain score at baseline, then dividing that value by the original baseline value and multiplying by 100% to get a percent change value.
Time frame: 60 minutes
Population: The discrepancy between the number of patients enrolled and randomized and the number analyzed is due to patient never being given IV opioids (13), enrolled twice (10), and missing primary outcome data (8)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hydromorphone | Number of Patients With 50% or Greater Decline in Pain Intensity Score From Baseline to 60 Minutes | 106 Participants |
| Usual Care | Number of Patients With 50% or Greater Decline in Pain Intensity Score From Baseline to 60 Minutes | 107 Participants |
Post Hoc
Number of Patients With a Pain Intensity Score of 3 or Less at 60 Minutes
Pain intensity is measured on the numerical rating scale (NRS) with scores ranging from 0 (no pain) to 10 (worst pain imaginable).
Time frame: 60 minutes
Population: The discrepancy between the number of patients enrolled and randomized and the number analyzed is due to patient never being given IV opioids (13), enrolled twice (10), and missing primary outcome data (8)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hydromorphone | Number of Patients With a Pain Intensity Score of 3 or Less at 60 Minutes | 83 Participants |
| Usual Care | Number of Patients With a Pain Intensity Score of 3 or Less at 60 Minutes | 87 Participants |
Post Hoc
Pain Intensity Score at 60 Minutes
Pain intensity is measured on the numerical rating scale (NRS) with scores ranging from 0 (no pain) to 10 (worst pain imaginable).
Time frame: 60 minutes
Population: The discrepancy between the number of patients enrolled and randomized and the number analyzed is due to patient never being given IV opioids (13), enrolled twice (10), and missing primary outcome data (8)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hydromorphone | Pain Intensity Score at 60 Minutes | 3 units on a scale |
| Usual Care | Pain Intensity Score at 60 Minutes | 3 units on a scale |